Chapter 3:

CARBOHYDRATES

OUTLINE

I. Carbohydrates Overview

II. Monosaccharides

III. Cyclic Structures of Monosaccharides

IV. Reactions of Monosaccharides

V. Disaccharides

VI. Oligosaccharides

VII.Acidic Polysaccharides

VIII.Structure and Roles of Polysaccharides

IX. Chemical Connections 2Chem 3 Intro to Biochemistry

• Each year, photosynthesis converts more than 100 billion metric tons of CO2 and H2O into cellulose and other plant products.

• act as storehouses of chemical energy (glucose, starch, glycogen)

• components of supportive structures in plants (cellulose), crustacean shells (chitin), and connective tissues in animals (acidic polysaccharides)

• essential components of nucleic acids (D-ribose and 2-deoxy-D-ribose)

3Chem 3 Intro to Biochemistry

Carbohydrates“the most abundant organic chemical in the plant world”

A. Structure and Nomenclature

• Carbohydrates means “hydrates of carbon ”

molecular formula (CH2O)n = (C . H2O)n

where n ≥ 3 or Cn(H2O)m

ex.

Glucose (blood sugar): C6H12O6

can also be written as C6(H2O)6

Sucrose (table sugar): C12H22O11

can also be written as C12(H2O)11

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CARBOHYDRATES

are polyhydroxyaldehydes, polyhydroxyketones, and their derivatives

all carbons attached to an oxygen

originate from solar-powered combination of CO2 + H2O in plants (photosynthesis)

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“saccharide” – derived from the Greek sakcharon;

Latin saccharum, meaning “sugar’.

MONOSACCHARIDES

have the general formula CnH2nOn

one of the carbons being the carbonyl group of either an aldehyde or a ketone

the suffix –ose indicates that the molecule is a carbohydrates

Prefixes tri-, tetra-, pent, etc indicate the number of carbon atoms in the chain.

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• Name the each of the following monosaccharides as an aldose or a ketose, and name each according to the number of carbon atoms.

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(a)(b)

(c)

Draw the structures of an aldotetrose and a ketopentose.

B. Fischer Projection Formulas

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devised by Hermann Emil Fischer in 1891

is a two-dimensional representation of a three-dimensional organic molecule by projection.

commonly designated using D,L system w/c is very common for sugars

– D,L designation refers to the configuration of

the highest-numbered asymmetric center

– D,L only refers the stereocenter of interest back

to D- and L glyceraldehyde

– D,L do not specify the sign of rotation of plane-

polarized light (that is d and l)

FISCHER PROJECTIONS

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D-glyceraldehydes (hydroxyl group at the highest numberedasymmetric carbon atom is written to the right):

L-glyceraldehydes (hydroxyl group at the highest numbered asymmetric carbon atom is written to the left):

D-Erythrose is the mirror image of L-Erythrose.

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• Draw Fischer projections for the four aldotetroses.Which are D-monosaccharides, which are L-monosaccharides, and which are enantiomers?

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(a)(b)

(c)

Based on the structure below, write the name of eachaldotetrose.

• Based on the structure below, write the write the name of each 2-ketopentose.

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(a)(b)

(c)

Draw Fischer projections for all 2-ketopentoses. Which are d-2-ketopentoses, which are L-2-ketopentoses, and which are enantiomers?

C. D- and L- Monosaccharides

• D-monosaccharide has the same configuration at its penultimate carbon as D-glyceraldehyde (its -OH group is on the right) in a Fischer projection

• L-monosaccharide has the same configuration at its penultimate carbon as L-glyceraldehyde (its -OH group is on the left).

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Aldotetrose Aldotriose

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Aldopentose

23Aldohexose

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Note C

numbering

1234

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THREE MOST ABUNDANT HEXOSES

1. D-glucose

Glucose, also known as dextrose, is found in largequantities throughout the living world. It is theprimary fuel for living cells. In animals, glucose isthe is the preferred energy source of brain cells andcell that have few or no mitochondria, such aerythrocytes. Cells that have a limited oxygensupply, such as those in the eyeball, also use largeamounts of glucose to generate energy. Dietarysources include plant starch and the disaccharideslactose, maltose and sucrose.

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THREE MOST ABUNDANT HEXOSES

2. D-galactose

Galactose is neccesary to synthesize a variety of

biomolecules. These include lactose (in lactating

mammary glands), glycolipids, certain

phospholipids, proteoglycans, and glycoproteins.

Synthesis of these substance is not diminished by

diets that lack galactose of the disaccharide

lactose .

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THREE MOST ABUNDANT HEXOSES

3. D-fructose

Fructose, or levulose, is often referred to as fruit sugarbecause of its high content in fruit. It is also found insome vegetables as well as in honey. This molecules isan important member of the ketose family of sugars. Ona per gram basis, fructose is twice as sweet as sucrose. Itcan therefore be used in smaller amounts. For thisreason, fructose is often used as sweetening agent inprocessed food products. Large amounts of fructose areused in the male reproductive tract. It is synthesized inthe seminal vesicles and then incorporated into semen.Sperm use the sugar as an energy source.

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Two sugars that differ in configuration at only one chiralcenter are epimers

D. Amino Sugars

• are monosaccharides in which an –OH group is replaced by an –NH2 group

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D. Amino Sugars

• Only three amino sugars are common in nature: D-glucosamine, D-mannosamine, and D-galactosamine.

• N- Acetyl-D-glucosamine, a derivative of D-glucosamine, is a component of many polysaccharides, including connective tissue such as cartilage.

• It is also a component of chitin, the hard, shell-like exoskeleton of lobsters, crabs, shrimp, and other shellfish.

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E. Physical Properties of Monosaccharides

• Monosaccharides are colorless, crystalline solids.

• All monosaccharides are very soluble in water because hydrogen bonding is possible between their polar -OH groups and water.

• They are only slightly soluble in ethanol.

• Insoluble in nonpolar solvents such as diethyl ether, dichloromethane, and benzene.

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Cyclic Structures of Monossacharides

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Cyclic Structures of Monossacharides

• Note cyclic hemiacetals form very readily when hydroxyland carbonyl groups are part of the same molecule and thattheir interaction produces a ring.

• 4-hydroxypentanal contains one stereocenter and thathemiacetal formation generates a second stereocenter atcarbon 1. 36

A. Haworth Projections

common way of representing the cyclic structure ofmonosaccharide

named after Sir Walter N. Haworth (1937)

in a Haworth projection, a five or six-membered cyclichemiacetal is represented as a planar pentagon orhexagon, respectively, lying roughly perpendicular tothe plane of the paper.

groups bonded to the carbons of the ring then lieeither above or below the plane of the ring.

A. Haworth Projections named after Sir Walter N. Haworth (1937)

Anomeric Carbon - the carbon atom which is involved in hemiacetal or acetal formation.The new carbon stereocenter created in forming the cyclic structure.

Anomers - stereoisomers formed when ring is formed (α, β).

A. Haworth Projections

Typically, Haworth projections are most commonly drawn with the anomeric carbon to the right and the hemiacetal oxygen to the back.

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In the terminology of carbohydrate chemistry,

β means that the -OH on the anomeric carbon of

the cyclic hemiacetal lies on the same side of the ring

as the terminal -CH2OH

α means that the -OH on the anomeric carbon of

the cyclic hemiacetal lies on the side of the ring

opposite from the terminal -CH2OH.

The α and β anomers of D-glucose interconvert in

aqueous solution by a process called mutarotation.

A. Haworth Projections

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The terms furanose and pyranose are used

because monosaccharide five- and six- membered

rings correspond to the heterocyclic compounds

furan and pyran.

A. Haworth Projections

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Aldopentoses Cyclic Conformation

• Draw Haworth projections for the α and βanomers of D-galactopyranose.

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Draw Haworth projections for the α and βanomers of D-galactopyranose.

The open-chain form of D-altrose, an aldohexoseisomer of glucose, has the following structure. Draw D-altrose in its cyclic hemiacetal form:

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The cyclic structure of D-mannose, an aldohexose, is drawn below. Convert this to the straight-chain Fischer projection structure.

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Ketohexoses Cyclic Formation

• Ketohexoses also occur in α and β anomeric forms. • In these compounds the hydroxyl group at C-5 (or C-6)

reacts with the keto group at C-2, forming a furanose (or pyranose) ring containing a hemiketal linkage

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β-D-glucopyranose – each group including the anomeric –OH group is equatorial.

α-D-glucopyranose - the anomeric –OH group is axial.51

B. Chair conformation

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Comparing the relative orientations of groups on the D-glucopyranose ring in the Haworth projection and the chair conformation.

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• Given the Fischer projection of the D-galactose, draw chair conformations for α-D-galactopyranose and β-D-galactopyranose. Label the anomeric carbon in each.

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• Given the Fischer projection of the D-galactose, draw chair conformations for α-D-galactopyranose and β-D-galactopyranose. Label the anomeric carbon in each.

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• the change in specific rotation that accompanies the equilibration of α and β anomers in aqueous solution.

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C. Mutarotation

•The equilibrium mixture consists of 64% β-D-glucopyranose and 36%

α-D-glucopyranose, with only a trace (0.003%) of the open-chain form.

Mutarotation is common to all carbohydrates that exist in hemiacetal

forms.

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The most stable form of glucose is β-D glucose.

REACTIONS OF MONOSACCHARIDES

A. Formation of Glycosides (Acetals)

B. Reduction to Alditols

C. Oxidation to Aldonic Acids (Reducing Sugars)

D. Oxidation to Uronic Acids

E. Formation of Phosphoric Esters

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A. Formation of Glycosides (Acetals)

Review

• Treatment of aldehyde or ketone with one molecule of alcohol yields a hemiacetal.

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Hemiacetal – a molecule containing a carbon bonded to one –OH group and one –OR group.

A. Formation of Glycosides (Acetals)

Review

• Hemiacetals can react further with alcohols to form acetalsplus water.

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Acetal – a molecule containing two –OR groups bonded to the same carbon.

A. Formation of Glycosides (Acetals)

Treatment of a monosaccharide – all forms of which exist almost exclusively as cyclic hemiacetals – with an alcohol also yields an acetal.

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Glycoside - a carbohydrate in which the --OH group on its anomeric

carbon is replaced by an --OR group.

Glycosidic bond - the bond from the anomeric carbon of a glycoside

to –OR group.

A. Formation of Glycosides (Acetals)

• Mutarotation is not possible in a glycoside because anacetal—unlike a hemiacetal—is no longer inequilibrium with the open-chain carbonyl containingcompound. Glycosides are stable in water andaqueous base; like other acetals, however, they arehydrolyzed in aqueous acid to an alcohol and amonosaccharide.

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Example : Finding the Anomeric Carbon and Glycosidic Bond

Draw the structural formula for methyl β-D-ribofuranoside(methyl β-D-riboside). Label the anomeric carbon and theglycosidic bond.

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FOLLOW –UP PROBLEM

Draw a Haworth projection and a chair conformation formethyl α-D-mannopyranoside (methyl α-D-mannoside).Label the anomeric carbon and the glycosidic bond.

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B. Reduction to Alditols The carbonyl group of a monosaccharide can be reduced to a

hydroxyl group by a variety of reducing agents, includinghydrogen in the presence of a transition metal catalyst andsodium borohydride.

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Alditols – the product formed when the CHO group of a

monosaccharide is reduced to a CH2OH group

B. Reduction to Alditols

• We name alditols by dropping the -ose from the name of the monosaccharide and adding -itol.

• Reduction of D-glucose gives D-glucitol, more commonly known as D-sorbitol.

• Sorbitol is found in the plant world in many berries and in cherries, plums, pears, apples, seaweed, and algae. It is about 60% as sweet as sucrose (table sugar) and is used in the manufacture of candies and as a sugar substitute for diabetics.

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B. Reduction to Alditols

• Other alditols commonly found in the biological world

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Xylitol is used as a sweetening agent in “sugarless” gum, candy,

and sweet cereals.

C. Oxidation to Aldonic Acids (Reducing Sugars)

Review

• Aldehydes (RCHO) are oxidized to carboxylic acids (RCOOH) by several agents, including oxygen, O2.

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C. Oxidation to Aldonic Acids (Reducing Sugars)

The aldehyde group of an aldose can be oxidized, under basic conditions, to a carboxylate group.

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• Any carbohydrate that reacts with an oxidizing agent to form an aldonic

acid is classified as a reducing sugar (it reduces the oxidizing agent).

C. Oxidation to Aldonic Acids (Reducing Sugars)

2-ketoses are also reducing sugars but carbon 1 (a CH2OH) of ketose is not oxidized directly. Instead, a 2-ketose exists in equilibrium with an aldose by way of an enediol intermediate.

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D. Oxidation to Uronic Acids

Enzyme-catalyzed oxidation of the primary alcohol at carbon 6 of a hexose yields a uronic acid.

72• D-glucuronic acid is widely distributed in both the plant and animal worlds.

D. Oxidation to Uronic Acids

•In humans, D-glucuronic acids serves as an importantcomponent of the acidic polysaccharides of connective tissues.The body also uses D-glucuronic acid to detoxify foreign phenolsand alcohols. In the liver, these compounds are converted toglycosides of glucuronic acid (glucuronides) and excreted in theurine. The intravenous anesthetic propofol, for example, isconverted to the following glucuronide and then excreted inurine:

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E. The Formation of Phosphoric Esters

• In the synthesis and metabolism of carbohydrates, theintermediates are very often not the sugars themselvesbut their phosphorylated derivatives.

• Condensation of phosphoric acid with one of the hydroxylgroups of a sugar forms a phosphate ester, as in glucose 6-phosphate.

• Sugar phosphates are relatively stable at neutral pH andbear a negative charge.

• One effect of sugar phosphorylation within cells is to trapthe sugar inside the cell; most cells do not have plasmamembrane transporters for phosphorylated sugars.

• Phosphorylation also activates sugars for subsequentchemical transformation.

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E. The Formation of Phosphoric Esters

Mono- and diphosphoric esters are important intermediates in the metabolism of monosaccharides.

75• D-glucuronic acid is widely distributed in both the plant and animal worlds.

DISACCHARIDES and OLIGOSACCHARIDES

Most carbohydrates in nature contain more than onemonosaccharide unit.

Disaccharides - a carbohydrate containing twomonosaccharide units joined by a glycosidic bond.

Oligosaccharides - a carbohydrate containing from six toten monossacharide units, each joined to the next by aglycosidic bond

Polysaccharide - a carbohydrate containing a large number of monosaccharide units, each joined to the next by one or more glycosidic bonds

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DISACCHARIDES • are carbohydrates containing 2 monossacharide units

joined together by glycosidic bond with the loss of water.

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Disaccharides Sources Monosaccharides

Maltose Germinating grains, Glucose + glucose

starch hydrolysis

Lactose Milk, yogurt, ice cream Glucose + galactose

Sucrose Sugar cane, sugar beets Glucose + fructose

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DISACCHARIDESA. Sucrose

• Sucrose (table sugar) is the most abundant disaccharide in thebiological world. It is obtained principally from the juice of sugarcane and sugar beets.

• In sucrose, carbon 1 of α-D-glucopyranose bonds to carbon 2of D-fructofuranose by an α-1,2-glycosidic bond.

• Because the anomeric carbons of both the glucopyranose andfructofuranose units are involved in formation of the glycosidicbond, neither monosaccharide unit is in equilibrium with itsopen-chain form. Thus sucrose is a nonreducing sugar.

• In the production of sucrose, sugar cane or sugar beet isboiled with water, and the resulting solution is cooled. Sucrosecrystals separate and are collected. Subsequent boiling toconcentrate the solution followed by cooling yields a dark, thicksyrup known as molasses.

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Monossacharide: GLUCOSE-FRUCTOSE

DISACCHARIDESA. Sucrose

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DISACCHARIDESB. Lactose

• Lactose is the principal sugar present in milk. It accounts for 5 to 8% of human milk and 4 to 6% of cow’s milk. • This disaccharide consists of D-galactopyranosebonded by a β-1,4-glycosidic bond to carbon 4 of D-glucopyranose. • Lactose is a reducing sugar, because the cyclic hemiacetal of the D-glucopyranose unit is in equilibrium with its open-chain form and can be oxidized to a carboxyl group.

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DISACCHARIDESB. Lactose

Monossacharide: GALACTOSE-GLUCOSE

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DISACCHARIDESC. Maltose

• Maltose derives its name from its presence in malt, the juice from sprouted barley and other cereal grains.

• It consists of two units of D-glucopyranose joined by a glycosidic bond between carbon 1 (the anomericcarbon) of one unit and carbon 4 of the other unit.

• Because the oxygen atom on the anomeric carbon of the first glucopyranose unit is alpha, the bond joining the two units is an a-1,4-glycosidic bond.

• Following are a Haworth projection and a chair conformation for β-maltose, so named because the -OH groups on the anomeric carbon of the glucose unit on the right are beta.

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DISACCHARIDESC. Maltose

Monossacharide: GLUCOSE-GLUCOSE

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DISACCHARIDESD. Relative Sweetness

The sweet taste of honey is due largely to D-fructose and D-glucose.

Lactose has almost no sweetness and is sometimes added to foods as

a filler. Some people cannot tolerate lactose well, however, and should

avoid these foods.

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Example: Drawing Chair Conformations for a Disaccharide

• Draw a chair conformation for the β anomer of adisaccharide in which two units of D-glucopyranose arejoined by an α-1,6-glycosidic bond.

FOLLOW –UP PROBLEM

Draw a chair conformation for the a form of adisaccharide in which two units of D-glucopyranoseare joined by a β-1,3-glycosidic bond.

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POLYSACCHARIDES

• Most carbohydrates found in nature occur as polysaccharides, polymers of medium to high molecular weight.

• Polysaccharides, also called glycans, differ from each other in the identity of their:

– recurring monosaccharide units,

– in the length of their chains,

– in the types of bonds

– linking the units,

– and in the degree of branching.87

POLYSACCHARIDES

• are long-chain polymers that contain large numbers of monosaccharides (usually glucose units) joined together by glycosidic bonds.

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Polysaccharides Sources Monosaccharides

Starch (amylose, Rice, wheat, Glucose

amylopectin grains, cereals

Glycogen Muscle, liver Glucose

Cellulose wood, plants, Glucose

paper, cotton

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A. Starch: Amylose and Amylopectin

POLYSACCHARIDES

A. Starch: Amylose and Amylopectin

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POLYSACCHARIDES

• Starch is used for energy storage in plants. It is found in all plant seeds and tubers and is the form in which glucose is stored for later use.

• Most starches contain 20 to 25% amylose and 75 to 80% amylopectin.

• Complete hydrolysis of both amylose and mylopectin yields only D-glucose.

A. Starch: Amylose

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A short segment of amylose, a linear polymer of D-glucose residues in (α1→4) linkage.

• A single chain can contain several thousand glucose residues to more than a million.

POLYSACCHARIDES

Amylose is composed of continuous, unbranched chains of as many as 4000 D-glucose units joined by α-1,4-glycosidic bonds.

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• Amylopectin has a high molecular weight (up to 100 million) but unlike amylose is highly branched.

• The glycosidic linkages joining successive glucose residues in amylopectin chains are (α1→4); the branch points (occurring every 24 to 30 residues) are (α 1 → 6) linkages.

A. Starch: Amylopectin

POLYSACCHARIDES

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• Glycogen constitutes up to 10% of liver mass and 1-2% of muscle mass• Glycogen is a polymer of glucose; similar to starch; also contains

(α1→4) and (α1→6) glycosidic bond• Only difference from starch: number of branches; it is more

extensively branched• (α1→6) branches every 8-12 residues

B. Glycogen

POLYSACCHARIDES

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POLYSACCHARIDES

• Cellulose is the most abundant natural polymer on earth

• The most widely distributed plant skeletal polysaccharide, constitutes almost half of the cell-wall material of wood.

• The principal strength and support for trees and plants

• Can also be soft and fuzzy (Ex. cotton is almost pure cellulose)

C. Cellulose

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POLYSACCHARIDES

• Cellulose molecules act much like stiff rods, acharacteristic that enables them to align themselves sideby side into well-organized, water-insoluble fibers inwhich the OH groups form numerous intermolecularhydrogen bonds.

• This arrangement of parallel chains in bundles givescellulose fibers their high mechanical strength. It alsoexplains why cellulose is insoluble in water. When a pieceof cellulose-containing material is placed in water, thereare not enough -OH groups on the surface of the fiber topull individual cellulose molecules away from thestrongly hydrogen-bonded fiber.

C. Cellulose

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(β1→4) linkages make

a big difference

Interchain H-bonding and intrasheet H-bonding produce supramolecular fiber of great tensile strength

C. Cellulose

POLYSACCHARIDES

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POLYSACCHARIDES

• Humans and other animals cannot use cellulose asfood because our digestive systems do not contain β-glucosidases, enzymes that catalyze the hydrolysis ofβ -glucosidic bonds.

• Instead, we have only α-glucosidases; hence, we usethe polysaccharides starch and glycogen as sources ofglucose.

• Glycogen and starch ingested in the diet arehydrolyzed by β-amylases, enzymes in saliva andintestinal secretions that break (α1→4) glycosidicbonds between glucose units.

C. Cellulose

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POLYSACCHARIDES

• Many bacteria and microorganisms do contain β-glucosidases and so can digest cellulose.

• Termites (much to our regret) have such bacteria intheir intestines and can use wood as their principalfood. Ruminants (cud-chewing animals) and horsescan also digest grasses and hay because β-glucosidase-containing microorganisms are present intheir alimentary systems.

C. Cellulose

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Acidic Polysaccharides

• Acidic polysaccharides are a group of polysaccharidesthat contain carboxyl groups and/or sulfuric estergroups.

• Acidic polysaccharides play important roles in thestructure and function of connective tissues.

• Because they contain amino sugars, a more currentname for these substances is glycosaminoglycans.

• Most connective tissues consist of collagen, astructural protein, combined with a variety of acidicpolysaccharides (glycosaminoglycans) that interact

• with collagen to form tight or loose networks.100

A. Hyaluronic Acid

• Hyaluronic acid is the simplest acidic polysaccharidepresent in connective tissue.

• It has a molecular weight of between 105 and 107g/mol and contains from 300 to 100,000 repeatingunits, depending on the organ in which it occurs.

• It is most abundant in embryonic tissues and inspecialized connective tissues such as synovial fluid,the lubricant of joints in the body, and the vitreous ofthe eye, where it provides a clear, elastic gel thatholds the retina in its proper position.

• Hyaluronic acid is also a common ingredient inlotions, moisturizers, and cosmetics. 101

A. Hyaluronic Acid • Hyaluronic acid is composed of D-glucuronic acid joined by a

b-1,3- glycosidic bond to N-acetyl-D-glucosamine, which is in turn linked to D-glucuronic acid by a b-1,4-glycosidic bond.

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B. Heparin • Heparin is a heterogeneous mixture of variably

sulfonated polysaccharide chains, ranging in molecularweight from 6000 to 30,000 g/mol.

• This acidic polysaccharide is synthesized and stored inmast cells (cells that are part of the immune system andthat occur in several types of tissues) of varioustissues—particularly the liver, lungs, and gut.

• Heparin has many biological functions, the best knownand fully understood of which is its anticoagulantactivity. It binds strongly to antithrombin III, a plasmaprotein involved in terminating the clotting process.

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B. Heparin • A heparin preparation with good anticoagulant activity

contains a minimum of eight repeating units.

• The larger the molecule, the greater its anticoagulantactivity. Because of this anticoagulant activity, it is widelyused in medicine.

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- a linear homopolysaccharide composed of N-acetylglucosamine residues in βlinkage

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